The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China.
General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China.
Proteomics Clin Appl. 2023 Sep;17(5):e2200102. doi: 10.1002/prca.202200102. Epub 2023 Mar 8.
Lactate was once considered to be a by-product of energy metabolism, but its unique biological value was only gradually explored with the advent of the Warburg effect. As an end product of glycolysis, lactate can act as a substrate for energy metabolism, a signal transduction molecule, a regulator of the tumor microenvironment and immune cells, and a regulator of the deubiquitination of specific enzymes, and is involved in various biological aspects of tumor regulation, including energy shuttling, growth and invasion, angiogenesis and immune escape. Furthermore, we describe a novel lactate-dependent epigenetic modification, namely histone lactylation modification, and review the progress of its study in tumors, mainly involving the reprogramming of tumor phenotypes, regulation of related gene expression, mediation of the glycolytic process in tumor stem cells (CSCs) and influence on the tumor immune microenvironment. The study of epigenetic regulation of tumor genes by histone modification is still in its infancy, and we expect that by summarizing the effects of lactate and histone modification on tumor and related gene regulation, we will clarify the scientific significance of future histone modification studies and the problems to be solved, and open up new fields for targeted tumor therapy.
乳酸曾被认为是能量代谢的副产物，但随着瓦博格效应的出现，其独特的生物学价值才逐渐被探索。作为糖酵解的终产物，乳酸可以作为能量代谢的底物、信号转导分子、肿瘤微环境和免疫细胞的调节剂、以及特定酶去泛素化的调节剂，参与肿瘤调控的各个生物学方面，包括能量穿梭、生长和侵袭、血管生成和免疫逃逸。此外，我们描述了一种新型的依赖于乳酸的表观遗传修饰，即组蛋白乳酸化修饰，并综述了其在肿瘤中的研究进展，主要涉及肿瘤表型的重编程、相关基因表达的调控、肿瘤干细胞（CSCs）中糖酵解过程的介导以及对肿瘤免疫微环境的影响。组蛋白修饰对肿瘤基因的表观遗传调控研究仍处于起步阶段，我们期望通过总结乳酸和组蛋白修饰对肿瘤及相关基因调控的作用，阐明未来组蛋白修饰研究的科学意义和需要解决的问题，为靶向肿瘤治疗开辟新的领域。
